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The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics

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Journal of biosciences and Medicines 2024年第8期12卷 347-356页

作者： robert b. Raffa Joseph V. Pergolizzi jr. School of Pharmacy (Emeritus) Temple University Philadelphia PA USA College of Pharmacy (Adjunct) University of Arizona Tucson AZ USA NEMA Research Naples FL USA

Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.

关键词： Chaperone Sigma-1 Receptor Energetics Thermodynamics Isothermal Titration Microcalorimetry

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim böttrich Pascal bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer robert Ringseis Klaus Eder Karsten Krüger Christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

Advances in discovery of novel investigational agents for functional cure of chronic hepatitis b:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： robert Lam Joseph K Lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis b virus(HbV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis b surface antigen(HbsAg)loss and suppression of HbV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis b,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HbsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis b virus Treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site

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Journal of Environmental Sciences 2024年第9期143卷 60-70页

作者： Hao Li Jun Yao Jianli Liu Ning Min Geoffrey Sunahara Dongyang Men robert Duran School of Water Resources and Environment Research Center of Environmental Science and EngineeringChina University of Geosciences(Beijing)Beijing 100083China Department of Natural Resource Sciences McGill University21111Lakeshore DriveSte-Anne-de-BellevueQuebecH9X 3V9Canada Equipe Environnement et Microbiologie MELODY groupUniversitéde Pau et des Pays de l’AdourE2S-UPPAIPREM UMR CNRS 5254BP 115564013 Pau CedexFrance

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological *** samples were collected from different depths(0 to 13 m)and analyzed for metal(loid)s content and fractionation,as well as microbial *** potential ecological risk indices for the different soil depths(ordered from high to low)were:1 m(D-1)>surface(S-0)>5 m(D-5)>13 m(D-13)>9 m(D-9),ranging between 1840.65-13,089.62,and representing extremely high environmental risks,of which Cd(and probably not arsenic)contributed to the highest environmental risk.A modified combined pollution risk index(MCR)combining total content and mobile proportion of metal(loid)s,and relative toxicities,was used to evaluate the degree of contamination and potential environmental *** the near-surface samples(S-0 and D-1 layers),the MCR considered that As,Cd,Pb,Sb,and Zn achieved high and alarming degrees of contamination,whereas Fe,Mn,and Ti were negligible or low to moderate pollution *** microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity *** analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics(pbial metabolic activity in the D-1 layer was low presumably due to heavy metal *** activity indicators and microcalorimetric growth rate(k)measurements were considered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

关键词： Abandoned chemical smelting sites Microbial activities Modified combined pollution risk Microcalorimetry Enzymatic activities

Coated boron layers by boronization and a real-time boron coating using an impurity powder dropper in the LHD

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Plasma Science and Technology 2024年第8期26卷 25-31页

作者： Naoko ASHIKAWA robert LUNSFORD Federico NESPOLI Erik GILSON Yaowei YU Jiansheng HU Shinichiro KADO National Institute for Fusion Science Toki 509-5292Japan Princeton Plasma Physics Laboratory Princeton NJ 08540United States of America Institute of Plasma Physics Chinese Academy of SciencesHefei 230031People’s Republic of China Institute of Advanced Energy Kyoto UniversityKyoto 611-0011Japan

In the Large Helical Device(LHD),diborane(b2H6)is used as a standard boron source for boronization,which is assisted by helium glow *** 2019,a new Impurity Powder Dropper(IPD)system was installed and is under evaluation as a real-time wall conditioning *** the LHD,which is a large-sized heliotron device,an additional helium(He)glow discharge cleaning(GDC)after boronization was operated for a reduction in hydrogen recycling from the coated boron *** operational time of 3 h was determined by spectroscopic data during glow discharges.A flat hydrogen profile is obtained on the top surface of the coated boron on the specimen exposed to *** results suggest a reduction in hydrogen at the top surface by *** oxygen in coated boron was obtained by boronization,and the coated boron,which has boron-oxide,on the first wall by b-IPD was also *** the difference in coating areas between b2H6 boronization and b-IPD operation,it would be most effective to use the IPD and b2H6 boronization coating together for optimized wall conditioning.

关键词： boron layer oxygen impurity hydrogen recycling impurity powder dropper LHD EAST

DeepRice: A deep learning and deep feature based classification of Rice leaf disease subtypes

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ARTIFICIAL INTELLIGENCE IN AGRICULTURE 2024年第1期11卷 34-49页

作者： Ritharson, P. Isaac Raimond, Kumudha Mary, X. Anitha robert, Jennifer Eunice Andrew, J. Karunya Inst Technol & Sci Dept CSE Coimbatore Tamilnadu India Karunya Inst Technol & Sci Dept Robot Engn Coimbatore India Manipal Acad Higher Educ Manipal Inst Technol Dept Mechatron Engn Manipal 576104 Karnataka India Manipal Acad Higher Educ Manipal Inst Technol Dept Comp Sci & Engn Manipal 576104 Karnataka India

Rice stands as a crucial staple food globally, with its enduring sustainability hinging on the prompt detection of rice leaf diseases. Hence, efficiently detecting diseases when they have already occurred holds paramount importance for solving the cost of manual visual identification and chemical testing. In the recent past, the identification of leaf pathologies in crops predominantly relies on manual methods using specialized equipment, which proves to be time-consuming and inefficient. This study offers a remedy by harnessing Deep Learning (DL) and transfer learning techniques to accurately identify and classify rice leaf diseases. A comprehensive dataset comprising 5932 self-generated images of rice leaves was assembled along with the benchmark datasets, categorized into 9 classes irrespective of the extent of disease spread across the leaves. These classes encompass diverse states including healthy leaves, mild and severe blight, mild and severe tungro, mild and severe blast, as well as mild and severe brown spot. Following meticulous manual labelling and dataset segmentation, which was validated by horticulture experts, data augmentation strategies were implemented to amplify the number of images. The datasets were subjected to evaluation using the proposed tailored Convolutional Neural Networks models. Their performance are scrutinized in conjunction with alternative transfer learning approaches like VGG16, Xception, ResNet50, DenseNet121, Inception ResnetV2, and Inception V3. The effectiveness of the proposed custom VGG16 model was gauged by its capacity to generalize to unseen images, yielding an exceptional accuracy of 99.94%, surpassing the benchmarks set by existing state-of-the-art models. Further, the layer wise feature extraction is also visualized as the interpretable AI. (c) 2023 The Authors. Publishing services by Elsevier b.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC bY-NC-ND license (http://creativeco

关键词： Rice leaf disease Deep learning CNN Crop yield Agriculture Food security IDENTIFICATION

Macroinvertebrate　assemblages　of　surface　mine　wetlands　of　Southwest　Virginia，USA

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Journal of Environmental Sciences 1996年第1期8卷 1-14页

作者： David H.Jones robert b. Atkinson John Cairns,jr.(Department of biology,Virginia Polytechnic Institute and State University, blacksburg,Virginia 24061 USA) Dept biol Virginia Poly Inst Blacksburg VA 24061 United States

The focus of this study was to investigate the macroinvertebrate community in surface mine wetlands. Nine wetlands were sampled for macroinvertebrates from July 1993 through May *** sites represented a range of physical,chemical, and biological parameters. Macroinvertebrates were found in all sites;a total of 14 orders, 40 families,and 70 genera were identified in the samples. Insects were the most common invertebrates,and most functional feeding groups were represented. Predators dominated with 63% of the taxa, followed by the collector/gathers with 20%,shredders 14%, and scrapers 3%. Sites differed in the number of taxa inhabiting *** ranged from 10 genera to *** lowest richness was found in two seasonal wetlands that were dry for the majority of the year. A permanently flooded site with no water quality problems and a dense growth of aquatic plants had the highest richness.

关键词： macroinvertebrate assemblages surface mine wetlands wetland faunas.

Effect of biochar Type and bradyrhizobium japonicum Seed Inoculation on Soybean Growth, Nodulation and Yield in a Tropical Ferric Acrisol

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Agricultural Sciences 2024年第6期15卷 635-675页

作者： Gbadebo Monday Elebiyo robert Thomas bachmann Department of Crop and Soil Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana branch Campus Malaysian Institute of Chemical and bio-Engineering Technology Green Chemistry and Sustainable Engineering Technology Cluster Universiti Kuala Lumpur Alor Gajah Malaysia

In tropical environments, most soybean growth studies have utilized rice husk biochar (RHb) in soil, even though it is low in nitrogen, potassium, and phosphorous. This may not give short-term agronomic performance relative to enriched biochar. Moreover, the impact of inoculating soybean seeds with atmospheric nitrogen-fixing bacterium bradyrhizobium japonicum on nodulation and grain yield has produced inconclusive findings in the literature. This research therefore aims to assess the effect of poultry manure (PM), poultry manure biochar (PMb) and RHb alone and in combinations on grain yield, dry shoot and root biomass of soybeans in the semi-deciduous agro-ecological zone. In addition, the effect of b. japonicum inoculated and non-inoculated soybean seeds on nodulation and grain yield was also investigated. The treatments followed a split plot design studying inoculation and non-inoculation, soil amendments (eight), and control subplot factors, respectively. The results show that the amendment of a ferric acrisol with 4 Mg∙ha−1 PM, 10 Mg∙ha−1 RHb + 2 Mg∙ha−1 PM, and 5 Mg∙ha−1 RHb + 4 Mg∙ha−1 PMb with b. japonicum inoculated seed produced significantly greater grain yield (p = 0.05). PM treatment had a significant (p b. japonicum-inoculated soybean seeds significantly (p = 0.014) increased soybean nodulation. This study suggests that RHb combined with PM or PMb provides a beneficial source of N, P, and K, resulting in improved soybean yield and nodulation in a tropical ferric acrisol.

关键词： biochar Poultry Manure Soil Fertility Soil Microorganism Soybean Production

Designing General Anesthetics That Have a better Safety Profile

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Pharmacology & Pharmacy 2019年第10期10卷 407-415页

作者： robert b. Raffa Joseph V. Pergolizzi jr. robert Taylor jr. Neumentum Inc.，Palo Alto CAUSA College of Pharmacy University of Arizona Tucson AZ USA Temple University School of Pharmacy Philadelphia PA USA NEMA Research Inc. Naples FL USA.

General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectively and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctive agents for surgical procedures. Nevertheless, they have potential adverse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in vulnerable populations such as the very young and the frail elderly. It would be desirable therefore to have alternative agents that are just as efficacious, but have a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (viz., an N-arylpyrrole derivative) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pave the way for new general anesthetics that are safer and easier to use.

关键词： General Anesthetic Intravenous Drug Discovery GAbAA Receptor Molecular Modeling